August 3, 2025 • 18 mins
Welcome back! Today, we will do a deeper dive on the signs and symptoms of Neurosyphilis. And was it responsible for Toyotomi Hideyoshi's behavioral changes in later life?
Sources:
https://www.psychiatrictimes.com/view/neurosyphilis-when-an-antipsychotic-is-not-enough
https://www.sciencedirect.com/science/article/pii/S0033318285728605
Mark as Played
Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
(00:00):
Hi y'all, so I just did an episode on Toyotomi Hideyoshi,
whose later life change and behavior I argued was possibly
due to later stage syphilis or neurosyphilis.
I got some good feedback on thatpart in particular, with one
listener asking for more detail on this very topic, so I decided
to make a dedicated episode on it.
So starting with the history, syphilis has probably been
(00:23):
around for thousands of years, with estimates around 7000 BC in
Southwest Asia and possibly spreading to Europe around 3000
BC. While the symptoms and course of
illness were apparent to us for some time, it was not identified
under the microscope until the earliest 20th century and later
(00:43):
confirmed by Japanese researcherHedeo Noguchi.
Many historical figures in the past were thought to or even
confirmed to have had it, like Ivan the Terrible, Nietzsche, Al
Capone, Howard Hughes, and if we're talking about military
figures, General Juno of the Napoleonic Wars is an
interesting and sad case. Before it was confirmed to be
(01:07):
caused by a bacterium, syphilis presentations used to be seen as
a weakness of character. Unfortunately.
Biologically, syphilis is a bacterium known as Treponema
pallidum, so that is its scientific name and it is
classified as a Spiro key due toits shape, which means that it
is long, slender and spiral shaped.
(01:31):
The most common cause of transmission is through sexual
contact and once infected, thereare different stages and
presentations of syphilis. So for example, you might have a
primary stage which might last three to four weeks, and typical
features include a painless ulcer, also known as Chanker, on
the skin. Secondary syphilis might take a
(01:53):
few months and is associated with a rash that may or may not
be only isolated to your palms and soles.
The infection may then be latentor hidden in your body for some
time, only to appear years to decades later.
And this is when things can become difficult.
And in terms of testing, there are different antibody tests
(02:15):
like RPRVDRL, FTA, A/B, S, etcetera, but the most accurate
test is confirmation with a lumbar puncture and
cerebrospinal fluid examination.Diagnosis with syphilis can be
very tricky because it has so many diverse presentations that
can look like other illnesses and so it's known as the great
(02:37):
imitator. After some time, syphilis can
cross the blood brain barrier and make its way into the
cerebrospinal fluid or CSF, essentially invading your
central nervous system. At this time it can cause
symptoms like headache, neck stiffness, sensory ataxia which
is basically a fancy word for coordination problems,
(02:59):
difficulty controlling bowel andbladder neuralgia or nerve pain
and Argyle Robertson pupils. So this is sometimes known
colloquially as prostitutes pupil.
So basically this is when your pupils constrict based on how
far the object is for accommodation but not to light.
It's estimated that anywhere from 25% to 40% of patients may
(03:23):
experience some kind of neuroinvasion during the course
of illness, and the risk is higher for those that go
untreated. And with this neuroinvasion,
psychiatric symptoms can developin the late stage of the
disease, which used to be known as general paresis of the insane
and accounted for a significant number of people in psychiatric
(03:44):
hospitals. So in fact, this was well
documented by the famous psychiatrist Emil Crapelin, who
published the book General Paresis in 1913.
Psychiatric symptoms seem seem to affect around 1/3 of patients
with neurosyphilis, with the most common being personality
changes, memory impairment, hostility, hallucinations, and
(04:06):
delusions. And so it can look a lot like
many types of dementia, especially frontal temporal
dementia. In fact, one source found that
20% of neurosyphilis cases had aprimary presentation of
dementia, whereas others have reported rates as high as 60% in
terms of personality changes. Because that's of primary
(04:28):
interest for this podcast, here are some of the most common
possible manifestations. These include loss of ambition
at work, irritability, decline in attention to personal
affairs, unusual giddiness, apathy, withdrawal, occasional
fits of temper, disregard for social and moral conventions,
(04:48):
moodiness, decreased interests, emotional ability, and sexual
indiscretion. Mechanistically, these symptoms
are secondary to the inflammatory and immune
responses from the infection rather than the primary
infection itself, as well as eventual neuronal damage.
Sometimes treatment wise, unfortunately antipsychotics
(05:09):
just don't work quite as well inthis population relative to
primary psychiatric disorders. And so the recommendation is to
treat the underlying disorder which is the syphilis.
So basically antibiotics and overall this has been very
successful. So just looking at the period
post World War 2 when antibiotics became more
widespread, the incidents decreased from 76 per 100,000
(05:31):
people in 1945 to 4 per 100,000 people almost a decade later.
And today syphilis is still around but at much lower rates
than before, and it's seen more frequently in individuals that
are immunocompromised, such as those coinfected with HIV.
The problem is that with later stage syphilis, like neuro
(05:53):
syphilis, a lot of times the damage is already done, so to
speak, so even penicillin or other antibiotics will not be
able to reverse the psychiatric manifestations.
Speaking from personal experience, if there are sudden
changes in personality, mood or psychosis with no history, no
family history, no substance useor very early or late onset
(06:16):
presentation, sometimes we'll try to rule out syphilis and
order antibiotic testing. We're not an order syphilis
antibody testing, not antibiotictesting.
Looking at the literature, syphilitic paresis should be
suspected when individuals have symptoms at a older age, have no
family history of mental health disorders, participate in high
(06:38):
risk sexual behavior, have one or more sexual partners who
tested positive for SD is and orhave a history of drug and
alcohol abuse. So to finish off this short
episode, I'm just going to add aclip from the last episode of me
speaking about the reasons why Ithink Toyotomi Hideyoshi's
erratic behavior in later life was a result of syphilis.
(07:01):
So here it is. Why did Hideyoshi, who is known
for being a cautious, careful, diplomatic, restrained man in
his younger years, all of a sudden become erratic,
impulsive, violent, with a decline in cognition in his
later years, which were not eventhat late because he died at 61
and he started having these symptoms in his 50s?
(07:22):
Well, let's go through all the possibilities.
Was it mania from bipolar disorder?
Because multiple sources I read use the word mania to describe
his later behavior. Well, based on the facts I have,
I would say very, very unlikely.First of all, the timeline just
doesn't match. First episode Mania typically
happens much earlier in life, usually late teens or early to
(07:46):
mid 20s, whereas we know that Hideyoshi's behavioral changes
happened in his 50s. Secondly, mania is typically
episodic for days, weeks, maybe in some cases months, often
followed by a crash into depression or at least a crash
into baseline. Hideyoshi's mood swings and
impulsivity, on the other hand, seem to start in his 50s and
(08:08):
gradually worsened over time. I also don't see any documented
changes in sleep patterns and energy, which are very
characteristic of mania. After all, you can think of
bipolar disorder as a disorder of circadian rhythm.
So if any of the listeners rightnow had to watch online lectures
as part of schooling or trainingin the past, and either because
(08:29):
they were really boring or it was the night before the exam
and you had to cram so you decided to put the lecture on
1.5 or two times speed, Well it it looks like they're talking
much faster and moving much faster than usual, right?
That's what many looks like and I just don't see it in
Hideyoshi. So very, very unlikely in my
opinion. OK, what about psychotic
(08:52):
depression? Well I mean this is possible
because Hideyoshi was very distressed after his first born
son Surumatsu died prematurely. Once Hideyori was born he seemed
to have a lot of paranoia and fear that his son would not be
supported and as a result executed many of those around
him, including his nephew and former heir Hitsugu.
(09:13):
The problem is, I wouldn't really call these delusions.
In fact, after his death spoilerHideyori is betrayed and
eventually killed by one of the men Hideyoshi entrusted to
mentor him. You can say his behavior was
erratic and cruel with poor judgement, but I have a hard
time calling these thoughts delusions.
So talking more about psychotic depression, it is more common in
(09:35):
later life and presents with delusions of guilt,
worthlessness, and theme often times and sometimes even
nihilistic in nature. So delusions involving death or
the world ending, something evenknown as Cotard's delusion is a
specific type of nihilistic delusion.
So this is when you think your body is rotting or even specific
parts or organs or decaying. Psychotic depression also
(09:58):
presents with anhedonia, which means difficulty feeling
pleasure. Sometimes psychosmotor slowing
as well. So this is a general slowing of
moving, speaking and thinking. Edioshi on the other hand was
described as being more labile. So a lot of shifts in mood with
impulsivity. I guess in summary, I, I just
don't think he had psychotic depression, you know, maybe
(10:21):
depressed mood from events like the death of his first born son,
but I don't think it was the primary cause for his erratic
behavior in late life. Maybe somewhat contributory, but
not primary. All right.
Next, what about dementia? Well, dementia or major
neurocognitive disorder is a very broad term.
(10:43):
There's a lot of different typesof dementia, and I'll go over
some of them quickly. Probably most famously is
Alzheimer's disease, thought to be due to a buildup of amyloid
plaques and neurofibrillary tangles in the brain.
Alzheimer's usually has a gradual onset, with cognitive
decline later in the illness especially.
(11:04):
There's also commonly psychosis later in the illness,
specifically paranoia, delusions, and hallucinations.
It can also affect personality, leading to impulsivity and poor
judgments. So so far a lot of this is
checking out, except timeline. It seems like Hiyoshi's decline
started in his 50s and he died at 61, which is much earlier
(11:26):
than usual. Alzheimer's dementia typically
doesn't present with a lot of the symptoms I mentioned until
usually 10 to 20 years later compared to Hiyoshi.
So usually you see it mid 60s, late 60s, early 70s, and this is
quite a bit later than when Hideoshi first had symptoms,
although they are definitely early onset variations.
Though rare. There are other types of
(11:49):
dementia like Lewy body disease dementia and Parkinson's disease
dementia which are characteristic of visual
hallucinations and resting tremor, and I don't see evidence
of either in Hideoshi. There's also vascular dementia,
which is secondary to impaired blood flow in the brain, such as
from strokes. This type of dementia, depending
on where the stroke is, often presents with movement
(12:12):
difficulties, facial weakness, etcetera, and decline occurs
very rapidly in noticeable drops.
So the buzzword we were taught in medical school was stepwise
fashion. So once again, I don't see any
obvious signs of this, and his declines seem to be more
gradual. So dementia overall, while
possible just the ones I've mentioned so far, Hedioshi
(12:35):
doesn't seem to fit well into. At least the most compelling
argument to me for Hideyoshi's change in behavior is that he
suffered from neurosyphilis, a later stage presentation of
syphilis if untreated. And there's actually a doctoral
thesis published on this very topic titled Methods and
Madness, the Last Years of Toyotomi Hideyoshi by David
(12:59):
Douglas Nielsen. So to talk about syphilis, it's
a bacterium that's often transmitted through sexual
activity and was likely first brought to Japan from the
Portuguese in the 1500s. It's been known as the great
imitator because it can cause somany different presentations
that will mimic other illnesses,including neurological and
psychiatric illnesses. The theory is based on many
(13:23):
aspects of Hideyoshi, so let's start with the basics.
So first, Hedyoshi was known to have produced a daughter quite
early in life, but I think before he met Nene, and then was
unable to produce any more biological children until his
late 50s with a single woman, Lady Cha Cha.
This is despite the fact that hehad numerous wives and
concubines, so at least 15 documented, but likely many many
(13:46):
more. There is some evidence that one
of Hideyoshi's concubines in midlife had syphilis and in fact
later went blind and became a nun, so this is a potential
source of infection for him. Untreated syphilis can possibly
lead to infertility, which wouldexplain the difficulty producing
biological children. But the question is how did he
have children with Lady Cha Cha then?
(14:09):
Well, this is actually hinted inthe 2024 TV show Shogun that
there were rumors even the yearsimmediately after Hideyoshi in
the Edo period that Lady Chacha was having an affair with her
foster brother, whom she was quite close with but not
biologically related to. And so Hideyori was hypothesized
to actually not be the biological child of Hideyoshi.
(14:32):
Obviously we don't know for sure.
I don't think there was genetic testing at that time, but the
fact that he himself admittedly had a weakness for women and was
having so many sexual relations with at least 15 women if not
more, and was only able to have two biological children passes
20s both the same woman makes itplausible, at least in my
(14:54):
opinion. So, moving on.
Next, let's talk about the behavioral changes.
Looking at a 2011 retrospective study from China, the most
common psychiatric presentationsof syphilis include personality
changes, dementia, abnormal behavior, and emotional
problems. So all things that Hideyoshi
seem to struggle with in his late life.
(15:16):
The paper also notes that depression, psychosis and mania
have also been noted as possiblesymptoms.
And in fact, in psychiatry, if there are sudden changes in
personality, mood, or psychosis with no history, no family
history, no substance use or very early or very late onset,
we'll actually do anti antibody testing for it sometimes.
(15:39):
Now the vast majority of the time it comes back negative.
In fact, I've probably only seenmaybe like one or two positive
tests in my entire life. But it's still good to rule out
in these cases. And obviously back in
Hideyoshi's day, there were no antibiotics.
So untreated syphilis would often involve into late
(15:59):
neurosyphilis, sometimes known as paretic neurosyphilis or
dementia paralytica. So a kind of dementia in itself.
Specifically, there are studies showing the similarities in
presentation between neurosyphilis and frontotemporal
dementia, which is characteristically associated
with personality changes and impulse control.
(16:20):
One of the most famous psychiatrists of all time was
Emil Crapelin, one of the greatest psychiatric minds I've
ever read about. So he lived in the, I think mid
late 19th century to the early 20th century, and he spent a lot
of his time observing and writing about syphilis and
actually compare the symptoms incourse of illness to other
(16:41):
psychiatric disorders like schizophrenia.
He wrote a book in 1913 titled General Paresis, and this book
is all about the neuropsychiatric manifestations
of syphilis and actually holds up pretty well over a century
later. The acronym paresis can describe
a lot of the symptoms of neurosyphilis.
So the P stands for personality,A for affect, R for reflexes, E
(17:06):
for I. So I didn't mention this before,
but syphilis can cause problems with constriction of pupils to
light, and this is known as Argyle Robertson pupil or
sometimes colloquially known as prostitutes pupil.
But anyway, S for sensorium, I for intellect, and S for speech.
Anyway, that was a lot and I spent a lot of time on this
(17:27):
topic, but I find this theory really really interesting and I
am somewhat convinced that hey, Yoshi's decline was due to
syphilis. Obviously, we'll never know, but
if you want to read up more on this topic, read up on Methods
and Madness, The Last Years of Toyota Mahidioshi because it's a
lot more detailed than what I presented regarding
(17:48):
neurosyphilis and the psychiatric manifestations.
I referenced a an article titledA Narrative Review of the Many
Psychiatric Manifestations of Neurosyphilis, The Great
Imitator. It's a pretty good article.
I'll link it in the notes if youwant to learn more about the
neuropsychiatric manifestations of syphilis.
So in conclusion, while we'll never know for sure, I think
(18:11):
it's plausible that hey, Yoshi suffered from syphilis and all
the proposed theories for the behavioral changes in his later
life. I think this is the one that's
most convincing to me, a sychiatrist.
Hi y'all, so I just did an episode on Toyotomi Hideyoshi,
whose later life change and behavior I argued was possibly
due to later stage syphilis or neurosyphilis.
I got some good feedback on thatpart in particular, with one
listener asking for more detail on this very topic, so I decided
to make a dedicated episode on it.
So starting with the history, syphilis has probably been
(00:23):
around for thousands of years, with estimates around 7000 BC in
Southwest Asia and possibly spreading to Europe around 3000
BC. While the symptoms and course of
illness were apparent to us for some time, it was not identified
under the microscope until the earliest 20th century and later
(00:43):
confirmed by Japanese researcherHedeo Noguchi.
Many historical figures in the past were thought to or even
confirmed to have had it, like Ivan the Terrible, Nietzsche, Al
Capone, Howard Hughes, and if we're talking about military
figures, General Juno of the Napoleonic Wars is an
interesting and sad case. Before it was confirmed to be
(01:07):
caused by a bacterium, syphilis presentations used to be seen as
a weakness of character. Unfortunately.
Biologically, syphilis is a bacterium known as Treponema
pallidum, so that is its scientific name and it is
classified as a Spiro key due toits shape, which means that it
is long, slender and spiral shaped.
(01:31):
The most common cause of transmission is through sexual
contact and once infected, thereare different stages and
presentations of syphilis. So for example, you might have a
primary stage which might last three to four weeks, and typical
features include a painless ulcer, also known as Chanker, on
the skin. Secondary syphilis might take a
(01:53):
few months and is associated with a rash that may or may not
be only isolated to your palms and soles.
The infection may then be latentor hidden in your body for some
time, only to appear years to decades later.
And this is when things can become difficult.
And in terms of testing, there are different antibody tests
(02:15):
like RPRVDRL, FTA, A/B, S, etcetera, but the most accurate
test is confirmation with a lumbar puncture and
cerebrospinal fluid examination.Diagnosis with syphilis can be
very tricky because it has so many diverse presentations that
can look like other illnesses and so it's known as the great
(02:37):
imitator. After some time, syphilis can
cross the blood brain barrier and make its way into the
cerebrospinal fluid or CSF, essentially invading your
central nervous system. At this time it can cause
symptoms like headache, neck stiffness, sensory ataxia which
is basically a fancy word for coordination problems,
(02:59):
difficulty controlling bowel andbladder neuralgia or nerve pain
and Argyle Robertson pupils. So this is sometimes known
colloquially as prostitutes pupil.
So basically this is when your pupils constrict based on how
far the object is for accommodation but not to light.
It's estimated that anywhere from 25% to 40% of patients may
(03:23):
experience some kind of neuroinvasion during the course
of illness, and the risk is higher for those that go
untreated. And with this neuroinvasion,
psychiatric symptoms can developin the late stage of the
disease, which used to be known as general paresis of the insane
and accounted for a significant number of people in psychiatric
(03:44):
hospitals. So in fact, this was well
documented by the famous psychiatrist Emil Crapelin, who
published the book General Paresis in 1913.
Psychiatric symptoms seem seem to affect around 1/3 of patients
with neurosyphilis, with the most common being personality
changes, memory impairment, hostility, hallucinations, and
(04:06):
delusions. And so it can look a lot like
many types of dementia, especially frontal temporal
dementia. In fact, one source found that
20% of neurosyphilis cases had aprimary presentation of
dementia, whereas others have reported rates as high as 60% in
terms of personality changes. Because that's of primary
(04:28):
interest for this podcast, here are some of the most common
possible manifestations. These include loss of ambition
at work, irritability, decline in attention to personal
affairs, unusual giddiness, apathy, withdrawal, occasional
fits of temper, disregard for social and moral conventions,
(04:48):
moodiness, decreased interests, emotional ability, and sexual
indiscretion. Mechanistically, these symptoms
are secondary to the inflammatory and immune
responses from the infection rather than the primary
infection itself, as well as eventual neuronal damage.
Sometimes treatment wise, unfortunately antipsychotics
(05:09):
just don't work quite as well inthis population relative to
primary psychiatric disorders. And so the recommendation is to
treat the underlying disorder which is the syphilis.
So basically antibiotics and overall this has been very
successful. So just looking at the period
post World War 2 when antibiotics became more
widespread, the incidents decreased from 76 per 100,000
(05:31):
people in 1945 to 4 per 100,000 people almost a decade later.
And today syphilis is still around but at much lower rates
than before, and it's seen more frequently in individuals that
are immunocompromised, such as those coinfected with HIV.
The problem is that with later stage syphilis, like neuro
(05:53):
syphilis, a lot of times the damage is already done, so to
speak, so even penicillin or other antibiotics will not be
able to reverse the psychiatric manifestations.
Speaking from personal experience, if there are sudden
changes in personality, mood or psychosis with no history, no
family history, no substance useor very early or late onset
(06:16):
presentation, sometimes we'll try to rule out syphilis and
order antibiotic testing. We're not an order syphilis
antibody testing, not antibiotictesting.
Looking at the literature, syphilitic paresis should be
suspected when individuals have symptoms at a older age, have no
family history of mental health disorders, participate in high
(06:38):
risk sexual behavior, have one or more sexual partners who
tested positive for SD is and orhave a history of drug and
alcohol abuse. So to finish off this short
episode, I'm just going to add aclip from the last episode of me
speaking about the reasons why Ithink Toyotomi Hideyoshi's
erratic behavior in later life was a result of syphilis.
(07:01):
So here it is. Why did Hideyoshi, who is known
for being a cautious, careful, diplomatic, restrained man in
his younger years, all of a sudden become erratic,
impulsive, violent, with a decline in cognition in his
later years, which were not eventhat late because he died at 61
and he started having these symptoms in his 50s?
(07:22):
Well, let's go through all the possibilities.
Was it mania from bipolar disorder?
Because multiple sources I read use the word mania to describe
his later behavior. Well, based on the facts I have,
I would say very, very unlikely.First of all, the timeline just
doesn't match. First episode Mania typically
happens much earlier in life, usually late teens or early to
(07:46):
mid 20s, whereas we know that Hideyoshi's behavioral changes
happened in his 50s. Secondly, mania is typically
episodic for days, weeks, maybe in some cases months, often
followed by a crash into depression or at least a crash
into baseline. Hideyoshi's mood swings and
impulsivity, on the other hand, seem to start in his 50s and
(08:08):
gradually worsened over time. I also don't see any documented
changes in sleep patterns and energy, which are very
characteristic of mania. After all, you can think of
bipolar disorder as a disorder of circadian rhythm.
So if any of the listeners rightnow had to watch online lectures
as part of schooling or trainingin the past, and either because
(08:29):
they were really boring or it was the night before the exam
and you had to cram so you decided to put the lecture on
1.5 or two times speed, Well it it looks like they're talking
much faster and moving much faster than usual, right?
That's what many looks like and I just don't see it in
Hideyoshi. So very, very unlikely in my
opinion. OK, what about psychotic
(08:52):
depression? Well I mean this is possible
because Hideyoshi was very distressed after his first born
son Surumatsu died prematurely. Once Hideyori was born he seemed
to have a lot of paranoia and fear that his son would not be
supported and as a result executed many of those around
him, including his nephew and former heir Hitsugu.
(09:13):
The problem is, I wouldn't really call these delusions.
In fact, after his death spoilerHideyori is betrayed and
eventually killed by one of the men Hideyoshi entrusted to
mentor him. You can say his behavior was
erratic and cruel with poor judgement, but I have a hard
time calling these thoughts delusions.
So talking more about psychotic depression, it is more common in
(09:35):
later life and presents with delusions of guilt,
worthlessness, and theme often times and sometimes even
nihilistic in nature. So delusions involving death or
the world ending, something evenknown as Cotard's delusion is a
specific type of nihilistic delusion.
So this is when you think your body is rotting or even specific
parts or organs or decaying. Psychotic depression also
(09:58):
presents with anhedonia, which means difficulty feeling
pleasure. Sometimes psychosmotor slowing
as well. So this is a general slowing of
moving, speaking and thinking. Edioshi on the other hand was
described as being more labile. So a lot of shifts in mood with
impulsivity. I guess in summary, I, I just
don't think he had psychotic depression, you know, maybe
(10:21):
depressed mood from events like the death of his first born son,
but I don't think it was the primary cause for his erratic
behavior in late life. Maybe somewhat contributory, but
not primary. All right.
Next, what about dementia? Well, dementia or major
neurocognitive disorder is a very broad term.
(10:43):
There's a lot of different typesof dementia, and I'll go over
some of them quickly. Probably most famously is
Alzheimer's disease, thought to be due to a buildup of amyloid
plaques and neurofibrillary tangles in the brain.
Alzheimer's usually has a gradual onset, with cognitive
decline later in the illness especially.
(11:04):
There's also commonly psychosis later in the illness,
specifically paranoia, delusions, and hallucinations.
It can also affect personality, leading to impulsivity and poor
judgments. So so far a lot of this is
checking out, except timeline. It seems like Hiyoshi's decline
started in his 50s and he died at 61, which is much earlier
(11:26):
than usual. Alzheimer's dementia typically
doesn't present with a lot of the symptoms I mentioned until
usually 10 to 20 years later compared to Hiyoshi.
So usually you see it mid 60s, late 60s, early 70s, and this is
quite a bit later than when Hideoshi first had symptoms,
although they are definitely early onset variations.
Though rare. There are other types of
(11:49):
dementia like Lewy body disease dementia and Parkinson's disease
dementia which are characteristic of visual
hallucinations and resting tremor, and I don't see evidence
of either in Hideoshi. There's also vascular dementia,
which is secondary to impaired blood flow in the brain, such as
from strokes. This type of dementia, depending
on where the stroke is, often presents with movement
(12:12):
difficulties, facial weakness, etcetera, and decline occurs
very rapidly in noticeable drops.
So the buzzword we were taught in medical school was stepwise
fashion. So once again, I don't see any
obvious signs of this, and his declines seem to be more
gradual. So dementia overall, while
possible just the ones I've mentioned so far, Hedioshi
(12:35):
doesn't seem to fit well into. At least the most compelling
argument to me for Hideyoshi's change in behavior is that he
suffered from neurosyphilis, a later stage presentation of
syphilis if untreated. And there's actually a doctoral
thesis published on this very topic titled Methods and
Madness, the Last Years of Toyotomi Hideyoshi by David
(12:59):
Douglas Nielsen. So to talk about syphilis, it's
a bacterium that's often transmitted through sexual
activity and was likely first brought to Japan from the
Portuguese in the 1500s. It's been known as the great
imitator because it can cause somany different presentations
that will mimic other illnesses,including neurological and
psychiatric illnesses. The theory is based on many
(13:23):
aspects of Hideyoshi, so let's start with the basics.
So first, Hedyoshi was known to have produced a daughter quite
early in life, but I think before he met Nene, and then was
unable to produce any more biological children until his
late 50s with a single woman, Lady Cha Cha.
This is despite the fact that hehad numerous wives and
concubines, so at least 15 documented, but likely many many
(13:46):
more. There is some evidence that one
of Hideyoshi's concubines in midlife had syphilis and in fact
later went blind and became a nun, so this is a potential
source of infection for him. Untreated syphilis can possibly
lead to infertility, which wouldexplain the difficulty producing
biological children. But the question is how did he
have children with Lady Cha Cha then?
(14:09):
Well, this is actually hinted inthe 2024 TV show Shogun that
there were rumors even the yearsimmediately after Hideyoshi in
the Edo period that Lady Chacha was having an affair with her
foster brother, whom she was quite close with but not
biologically related to. And so Hideyori was hypothesized
to actually not be the biological child of Hideyoshi.
(14:32):
Obviously we don't know for sure.
I don't think there was genetic testing at that time, but the
fact that he himself admittedly had a weakness for women and was
having so many sexual relations with at least 15 women if not
more, and was only able to have two biological children passes
20s both the same woman makes itplausible, at least in my
(14:54):
opinion. So, moving on.
Next, let's talk about the behavioral changes.
Looking at a 2011 retrospective study from China, the most
common psychiatric presentationsof syphilis include personality
changes, dementia, abnormal behavior, and emotional
problems. So all things that Hideyoshi
seem to struggle with in his late life.
(15:16):
The paper also notes that depression, psychosis and mania
have also been noted as possiblesymptoms.
And in fact, in psychiatry, if there are sudden changes in
personality, mood, or psychosis with no history, no family
history, no substance use or very early or very late onset,
we'll actually do anti antibody testing for it sometimes.
(15:39):
Now the vast majority of the time it comes back negative.
In fact, I've probably only seenmaybe like one or two positive
tests in my entire life. But it's still good to rule out
in these cases. And obviously back in
Hideyoshi's day, there were no antibiotics.
So untreated syphilis would often involve into late
(15:59):
neurosyphilis, sometimes known as paretic neurosyphilis or
dementia paralytica. So a kind of dementia in itself.
Specifically, there are studies showing the similarities in
presentation between neurosyphilis and frontotemporal
dementia, which is characteristically associated
with personality changes and impulse control.
(16:20):
One of the most famous psychiatrists of all time was
Emil Crapelin, one of the greatest psychiatric minds I've
ever read about. So he lived in the, I think mid
late 19th century to the early 20th century, and he spent a lot
of his time observing and writing about syphilis and
actually compare the symptoms incourse of illness to other
(16:41):
psychiatric disorders like schizophrenia.
He wrote a book in 1913 titled General Paresis, and this book
is all about the neuropsychiatric manifestations
of syphilis and actually holds up pretty well over a century
later. The acronym paresis can describe
a lot of the symptoms of neurosyphilis.
So the P stands for personality,A for affect, R for reflexes, E
(17:06):
for I. So I didn't mention this before,
but syphilis can cause problems with constriction of pupils to
light, and this is known as Argyle Robertson pupil or
sometimes colloquially known as prostitutes pupil.
But anyway, S for sensorium, I for intellect, and S for speech.
Anyway, that was a lot and I spent a lot of time on this
(17:27):
topic, but I find this theory really really interesting and I
am somewhat convinced that hey, Yoshi's decline was due to
syphilis. Obviously, we'll never know, but
if you want to read up more on this topic, read up on Methods
and Madness, The Last Years of Toyota Mahidioshi because it's a
lot more detailed than what I presented regarding
(17:48):
neurosyphilis and the psychiatric manifestations.
I referenced a an article titledA Narrative Review of the Many
Psychiatric Manifestations of Neurosyphilis, The Great
Imitator. It's a pretty good article.
I'll link it in the notes if youwant to learn more about the
neuropsychiatric manifestations of syphilis.
So in conclusion, while we'll never know for sure, I think
(18:11):
it's plausible that hey, Yoshi suffered from syphilis and all
the proposed theories for the behavioral changes in his later
life. I think this is the one that's
most convincing to me, a sychiatrist.
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